Genetic Variant ABCG2:c.1738-46G>A (chr4-88094705-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004827.3(ABCG2):c.1738-46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 1,483,750 control chromosomes in the GnomAD database, including 507,112 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.68 ( 39400 hom., cov: 32)

Exomes 𝑓: 0.83 ( 467712 hom. )

Consequence

ABCG2
NM_004827.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.467

Publications

36 publications found

Variant links:

Genes affected

ABCG2 (HGNC:74): (ATP binding cassette subfamily G member 2 (JR blood group)) The membrane-associated protein encoded by this gene is included in the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. Alternatively referred to as a breast cancer resistance protein, this protein functions as a xenobiotic transporter which may play a major role in multi-drug resistance. It likely serves as a cellular defense mechanism in response to mitoxantrone and anthracycline exposure. Significant expression of this protein has been observed in the placenta, which may suggest a potential role for this molecule in placenta tissue. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ABCG2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004827.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ABCG2	NM_004827.3	MANE Select	c.1738-46G>A	intron	N/A	NP_004818.2	Q9UNQ0-1
ABCG2	NM_001348985.1		c.1738-46G>A	intron	N/A	NP_001335914.1	Q9UNQ0-1
ABCG2	NM_001348986.2		c.1738-46G>A	intron	N/A	NP_001335915.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ABCG2	ENST00000237612.8	TSL:1 MANE Select	c.1738-46G>A	intron	N/A	ENSP00000237612.3	Q9UNQ0-1
ABCG2	ENST00000515655.5	TSL:1	c.1728-46G>A	intron	N/A	ENSP00000426917.1	Q9UNQ0-2
ABCG2	ENST00000889086.1		c.1825-46G>A	intron	N/A	ENSP00000559145.1

Frequencies

GnomAD3 genomes

AF:

0.678

AC:

103076

AN:

152042

Hom.:

39407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.777

Gnomad AMR

AF:

0.630

Gnomad ASJ

AF:

0.885

Gnomad EAS

AF:

0.533

Gnomad SAS

AF:

0.773

Gnomad FIN

AF:

0.881

Gnomad MID

AF:

0.803

Gnomad NFE

AF:

0.866

Gnomad OTH

AF:

0.715

GnomAD2 exomes

AF:

0.751

AC:

185059

AN:

246320

AF XY:

0.774

show subpopulations

Gnomad AFR exome

AF:

0.301

Gnomad AMR exome

AF:

0.525

Gnomad ASJ exome

AF:

0.894

Gnomad EAS exome

AF:

0.532

Gnomad FIN exome

AF:

0.883

Gnomad NFE exome

AF:

0.869

Gnomad OTH exome

AF:

0.799

GnomAD4 exome

AF:

0.829

AC:

1104531

AN:

1331590

Hom.:

467712

Cov.:

AF XY:

0.832

AC XY:

557150

AN XY:

669684

show subpopulations

African (AFR)

AF:

0.300

AC:

9100

AN:

30366

American (AMR)

AF:

0.537

AC:

23556

AN:

43894

Ashkenazi Jewish (ASJ)

AF:

0.893

AC:

22543

AN:

25230

East Asian (EAS)

AF:

0.549

AC:

21361

AN:

38904

South Asian (SAS)

AF:

0.796

AC:

65841

AN:

82754

European-Finnish (FIN)

AF:

0.886

AC:

47186

AN:

53264

Middle Eastern (MID)

AF:

0.831

AC:

4572

AN:

5502

European-Non Finnish (NFE)

AF:

0.870

AC:

865977

AN:

995792

Other (OTH)

AF:

0.794

AC:

44395

AN:

55884

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

8247

16494

24740

32987

41234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18008

36016

54024

72032

90040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.678

AC:

103091

AN:

152160

Hom.:

39400

Cov.:

AF XY:

0.679

AC XY:

50504

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.318

AC:

13203

AN:

41472

American (AMR)

AF:

0.629

AC:

9603

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.885

AC:

3074

AN:

3472

East Asian (EAS)

AF:

0.534

AC:

2760

AN:

5172

South Asian (SAS)

AF:

0.774

AC:

3730

AN:

4820

European-Finnish (FIN)

AF:

0.881

AC:

9354

AN:

10616

Middle Eastern (MID)

AF:

0.788

AC:

230

AN:

292

European-Non Finnish (NFE)

AF:

0.866

AC:

58924

AN:

68016

Other (OTH)

AF:

0.711

AC:

1504

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1224

2447

3671

4894

6118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

778

1556

2334

3112

3890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.771

Hom.:

102476

Bravo

AF:

0.637

Asia WGS

AF:

0.623

AC:

2171

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.57

PhyloP100

-0.47

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over